title: LINE-1 retrotransposable element DNA accumulates in HIV-1-infected cells.
abstract: Type 1 long-interspersed nuclear elements (L1s) are autonomous retrotransposable elements that retain the potential for activity in the human genome but are suppressed by host factors. Retrotransposition of L1s into chromosomal DNA can lead to genomic instability, whereas reverse transcription of L1 in the cytosol has the potential to activate innate immune sensors. We hypothesized that HIV-1 infection would compromise cellular control of L1 elements, resulting in the induction of retrotransposition events. Here, we show that HIV-1 infection enhances L1 retrotransposition in Jurkat cells in a Vif- and Vpr-dependent manner. In primary CD4(+) cells, HIV-1 infection results in the accumulation of L1 DNA, at least the majority of which is extrachromosomal. These data expose an unrecognized interaction between HIV-1 and endogenous retrotransposable elements, which may have implications for the innate immune response to HIV-1 infection, as well as for HIV-1-induced genomic instability and cytopathicity.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R Brad
authors.initials: RB
authors.lastname: Jones
authors.forename: Haihan
authors.initials: H
authors.lastname: Song
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Keith E
authors.initials: KE
authors.lastname: Garrison
authors.forename: Anton A
authors.initials: AA
authors.lastname: Buzdin
authors.forename: Naveed
authors.initials: N
authors.lastname: Anwar
authors.forename: Diana V
authors.initials: DV
authors.lastname: Hunter
authors.forename: Shariq
authors.initials: S
authors.lastname: Mujib
authors.forename: Vesna
authors.initials: V
authors.lastname: Mihajlovic
authors.forename: Eric
authors.initials: E
authors.lastname: Martin
authors.forename: Erika
authors.initials: E
authors.lastname: Lee
authors.forename: Monika
authors.initials: M
authors.lastname: Kuciak
authors.forename: Rui André Saraiva
authors.initials: RA
authors.lastname: Raposo
authors.forename: Ardalan
authors.initials: A
authors.lastname: Bozorgzad
authors.forename: Duncan A
authors.initials: DA
authors.lastname: Meiklejohn
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Mario A
authors.initials: MA
authors.lastname: Ostrowski
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1